2007 Grant - Fernandez-Funez

New Genetic Suppressors of Beta-Amyloid Neurotoxicity

2007 New Investigator Research Grant

Beta-amyloid, a tiny protein fragment, may play a key role in damaging cell-to-cell communication and causing the loss of brain cells in Alzheimer's disease. The fragment tends to clump together in stages, eventually forming plaques within the Alzheimer brain. One of the early stages in this clumping process—a cluster of a few amyloid molecules called an oligomer—may be the most toxic form of beta-amyloid. Yet scientists know little about how the protein fragment creates these toxic clumps.

In preliminary research, Pedro Fernandez-Funez, Ph.D., and colleagues have identified 20 genes that block toxic beta-amyloid clumping in fruit flies. These flies have been engineered to develop Alzheimer-like symptoms. The genes appear to activate enzymes that can degrade beta-amyloid before it accumulates.

For their proposed grant, Dr. Fernandez-Funez and colleagues will conduct further tests with fruit flies to better understand the mechanisms behind how the 20 genes modify beta-amyloid. Their work will focus on one particular gene that appears to have an especially powerful ability to block toxic beta-amyloid forms. The team will then determine whether this and the other candidate genes possess similar amyloid-suppressing abilities in human nerve cell cultures.

Results of this study should lead to a better understanding of how beta-amyloid becomes toxic and contributes to Alzheimer's disease. Such knowledge could lead to more effective therapies for stopping or delaying the progression of the disease.